tbuckley/cabot-search huggingface dataset:
Moving towards vertically integrated artificial intelligence development
Authors: Joe Zhang, Sanjay Budhdeo, Wasswa William, Paul Cerrato, Haris Shuaib, Harpreet Sood, Hutan Ashrafian, John Halamka, James T. Teo
Journal: npj Digital Medicine (2022)

Substantial interest and investment in clinical artificial intelligence (AI) research has not resulted in widespread translation to deployed AI solutions. Current attention has focused on bias and explainability in AI algorithm development, external validity and model generalisability, and lack of equity and representation in existing data. While of great importance, these considerations also reflect a model-centric approach seen in published clinical AI research, which focuses on optimising architecture and performance of an AI model on best available datasets. However, even robustly built models using state-of-the-art algorithms may fail once tested in realistic environments due to unpredictability of real-world conditions, out-of-dataset scenarios, characteristics of deployment infrastructure, and lack of added value to clinical workflows relative to cost and potential clinical risks. In this perspective, we define a vertically integrated approach to AI development that incorporates early, cross-disciplinary, consideration of impact evaluation, data lifecycles, and AI production, and explore its implementation in two contrasting AI development pipelines: a scalable "AI factory" (Mayo Clinic, Rochester, United States), and an end-to-end cervical cancer screening platform for resource poor settings (Paps AI, Mbarara, Uganda). We provide practical recommendations for implementers, and discuss future challenges and novel approaches (including a decentralised federated architecture being developed in the NHS (AI4VBH, London, UK)). Growth in global clinical AI research continues unabated, and introduction of vertically integrated teams and development practices can increase the translational potential of future clinical AI projects.
Error in Discussion
Journal: JAMA Network Open (2022)

Ruth A. Karron, MD; Marissa K. Hetrich, MHS; Yu Bin Na, MSPH; Maria Deloria Knoll, PhD; Elizabeth Schappell, MSN; Jennifer Meece, PhD; Erika Hanson, MS; Suxiang Tong, PhD; Justin S. Lee, PhD; Vic Veguilla, PhD; Fatimah S. Dawood, MD; SEARCH Study Team; Christine Council-DiBitetto; Milena Gatto; Maria Garcia-Quesada; Tina Ghasri; Amanda Gormley; Kyley Guenther; Kristi Herbert; Maria Jordan; Karen Loehr; Jason Morsell; Jennifer Oliva; Jocelyn San Mateo; Khadija Smith; Kimberli Wanionek; Cathleen Weadon; Suzanne Woods; Yan Li; Anna Kelleher; Anna Uehara; Ying Tao; Jing Zhang; Brian Lynch; Meghan Bentz; Alex Burgin; Mark Burroughs; Morgan L. Davis; Joseph C. Madden; Sarah Nobles; Jasmine Padilla; Mili Sheth; Dhwani Bhatra; Jason Caravas; Peter Cook; Dakota Howard; Kristine Lacek; Clint Paden; Ben Rambo-Martin; Samuel Shepard
Human immunomodulatory ligand B7-1 mediates synaptic remodeling via the p75 neurotrophin receptor
Authors: Nicholas C. Morano, Roshelle S. Smith, Victor Danelon, Ryan Schreiner, Uttsav Patel, Natalia G. Herrera, Carla Smith, Steven M. Olson, Michelle K. Laerke, Alev Celikgil, Scott J. Garforth, Sarah C. Garrett-Thomson, Francis S. Lee, Barbara L. Hempstead, Steven C. Almo
Journal: Journal of Clinical Investigation (2022)

Cell surface receptors, ligands, and adhesion molecules underlie development, circuit formation, and synaptic function of the central nervous system and represent important therapeutic targets for many neuropathologies. The functional contributions of interactions between cell surface proteins of neurons and nonneuronal cells have not been fully addressed. Using an unbiased protein-protein interaction screen, we showed that the human immunomodulatory ligand B7-1 (hB7-1) interacts with the p75 neurotrophin receptor (p75NTR) and that the B7-1:p75NTR interaction is a recent evolutionary adaptation present in humans and other primates, but absent in mice, rats, and other lower mammals. The surface of hB7-1 that engages p75NTR overlaps with the hB7-1 surface involved in CTLA-4/CD28 recognition, and these molecules directly compete for binding to p75NTR. Soluble or membrane-bound hB7-1 altered dendritic morphology of cultured hippocampal neurons, with loss of the postsynaptic protein PSD95 in a p75NTR-dependent manner. Abatacept, an FDA-approved therapeutic (CTLA-4-hFc fusion) inhibited these processes. In vivo injection of hB7-1 into the murine subiculum, a hippocampal region affected in Alzheimer's disease, resulted in p75NTR-dependent pruning of dendritic spines. Here, we report the biochemical interaction between B7-1 and p75NTR, describe biological effects on neuronal morphology, and identify a therapeutic opportunity for treatment of neuroinflammatory diseases.
Amorphous Ultra‐Small Fe‐Based Nanocluster Engineered and ICG Loaded Organo‐Mesoporous Silica for GSH Depletion and Photothermal‐Chemodynamic Synergistic Therapy
Authors: Jiaqi Li, Haina Tian, Fukai Zhu, Suhua Jiang, Maomao He, Yang Li, Qiang Luo, Wen Sun, Xiaolong Liu, Peiyuan Wang
Journal: Advanced Healthcare Materials (2022)

Abstract Intracellular oxidative amplification can effectively destroy tumor cells. Additionally, Fe‐mediated Fenton reaction often converts cytoplasm H 2 O 2 to generate extensive hypertoxic hydroxyl radical ( • OH), leading to irreversible mitochondrion damage for tumor celleradication, which is widely famous as tumor chemodynamic therapy (CDT). Unfortunately, intracellular overexpressed glutathione (GSH) always efficiently scavenges • OH, resulting in the significantly reduced CDT effect. To overcome this shortcoming and improve the oxidative stress in cytoplasm, Fe 3 O 4 ultrasmall nanoparticle encapsulated and ICG loaded organo‐mesoporous silica nanovehicles (omSN@Fe‐ICG) are constructed to perform both photothermal and GSH depletion to enhance the Fenton‐like CDT, by realizing intracellular oxidative stress amplification. After this nanoagents are internalized, the tetrasulfide bonds in the dendritic mesoporous framework can be decomposed with GSH to amplify the toxic ROS neration by selectively converting H 2 O 2 to hydroxyl radicals through the released Fe‐based nanogranules. Furthermore, the NIR laser‐induced hyperthermia can further improve the Fenton reaction rate that simultaneously destroyed the mitochondria. As a result, the GSH depletion and photothermal assisted CDT can remarkably improve the tumor eradication efficacy.
Spatial Analysis of Changes in Cigarette Sales in Massachusetts and Bordering States Following the Massachusetts Menthol Flavor Ban
Authors: Samuel Asare, Anuja Majmundar, J. Lee Westmaas, Priti Bandi, Zheng Xue, Ahmedin Jemal, Nigar Nargis
Journal: JAMA Network Open (2022)

This cohort study examines changes in cigarette sales in Massachusetts and its bordering states following a comprehensive ban on menthol flavor in Massachusetts in 2020.
Correction: First-in-Class Anti-immunoglobulin–like Transcript 4 Myeloid-Specific Antibody MK-4830 Abrogates a PD-1 Resistance Mechanism in Patients with Advanced Solid Tumors
Authors: Lillian L. Siu, Ding Wang, John Hilton, Ravit Geva, Drew Rasco, Ruth Perets, Anson K. Abraham, Douglas C. Wilson, Julia F. Markensohn, Jared Lunceford, Leah Suttner, Shabana Siddiqi, Rachel A. Altura, Corinne Maurice-Dror
Journal: Clinical Cancer Research (2022)

In the original version of this article (1), the Spearman correlations were correct in the text and incorrect in Fig. 4. The figure has been corrected in the latest online HTML and PDF versions of the article. The authors regret the error.
Two-Year Health Outcomes in Hospitalized COVID-19 Survivors in China
Authors: Xinyue Yang, Chao Hou, Ye Shen, Mingyang Zhang, Kejun Zhang, Fang Wang, Yuhui Liu, Xiangyu Ma, Lixia Cheng, Jun Kang, Baoman Hu, Man Wang, Ling Zeng, Yanjiang Wang, Yong He, Guoqiang Cao, Jianxin Jiang, Paul Jones, Bin Cao, Li Li
Journal: JAMA Network Open (2022)

Importance Relatively little is known about the persistence of symptoms in patients with COVID-19 for more than 1 year after their acute illness. Objective To assess the health outcomes among hospitalized COVID-19 survivors over 2 years and to identify factors associated with increased risk of persistent symptoms. Design, Setting, and Participants This was a longitudinal cohort study of patients who survived COVID-19 at 2 COVID-19–designated hospitals in Wuhan, China, from February 12 to April 10, 2020. All patients were interviewed via telephone at 1 year and 2 years after discharge. The 2-year follow-up study was conducted from March 1 to April 6, 2022. Statistical analysis was conducted from April 20 to May 5, 2022. The severity of disease was defined by World Health Organization guideline for COVID-19. Exposures COVID-19. Main Outcomes and Measures The main outcome was symptom changes over 2 years after hospital discharge. All patients completed a symptom questionnaire for evaluation of symptoms, along with a chronic obstructive pulmonary disease assessment test (CAT) at 1-year and 2-year follow-up visits. Results Of 3988 COVID-19 survivors, a total of 1864 patients (median [IQR] age, 58.5 [49.0-68.0] years; 926 male patients [49.7%]) were available for both 1-year and 2-year follow-up visits. The median (IQR) time from discharge to follow-up at 2 years was 730 (719-743) days. At 2 years after hospital discharge, 370 patients (19.8%) still had symptoms, including 224 (12.0%) with persisting symptoms and 146 (7.8%) with new-onset or worsening of symptoms. The most common symptoms were fatigue, chest tightness, anxiety, dyspnea, and myalgia. Most symptoms resolved over time, but the incidence of dyspnea showed no significant change (1-year vs 2-year, 2.6% [49 patients] vs 2.0% [37 patients]). A total of 116 patients (6.2%) had CAT total scores of at least 10 at 2 years after discharge. Patients who had been admitted to the intensive care unit had higher risks of persistent symptoms (odds ratio, 2.69; 95% CI, 1.02-7.06; P = .04) and CAT scores of 10 or higher (odds ratio, 2.83; 95% CI, 1.21-6.66; P = .02). Conclusions and Relevance In this cohort study, 2 years after hospital discharge, COVID-19 survivors had a progressive decrease in their symptom burden, but those with severe disease during hospitalization, especially those who required intensive care unit admission, had higher risks of persistent symptoms. These results are related to the original strain of the virus, and their relevance to infections with the Omicron variant is not known.
Computational benchmarking of putative KIFC1 inhibitors
Authors: Nivya Sharma, Dani Setiawan, Donald Hamelberg, Rishikesh Narayan, Ritu Aneja
Journal: Medicinal Research Reviews (2022)

Abstract The centrosome in animal cells is instrumental in spindle pole formation, nucleation, proper alignment of microtubules during cell division, and distribution of chromosomes in each daughter cell. Centrosome amplification involving structural and numerical abnormalities in the centrosome can cause chromosomal instability and dysregulation of the cell cycle, leading to cancer development and metastasis. However, disturbances caused by centrosome amplification can also limit cancer cell survival by activating mitotic checkpoints and promoting mitotic catastrophe. As a smart escape, cancer cells cluster their surplus of centrosomes into pseudo‐bipolar spindles and progress through the cell cycle. This phenomenon, known as centrosome clustering (CC), involves many proteins and has garnered considerable attention as a specific cancer cell‐targeting weapon. The kinesin‐14 motor protein KIFC1 is a minus end‐directed motor protein that is involved in CC. Because KIFC1 is upregulated in various cancers and modulates oncogenic signaling cascades, it has emerged as a potential chemotherapeutic target. Many molecules have been identified as KIFC1 inhibitors because of their centrosome declustering activity in cancer cells. Despite the ever‐increasing literature in this field, there have been few efforts to review the progress. The current review aims to collate and present an in‐depth analysis of known KIFC1 inhibitors and their biological activities. Additionally, we present computational docking data of putative KIFC1 inhibitors with their binding sites and binding affinities. This first‐of‐kind comparative analysis involving experimental biology, chemistry, and computational docking of different KIFC1 inhibitors may help guide decision‐making in the selection and design of potent inhibitors.
Geospatial Analysis of Organ Transplant Referral Regions
Authors: Tyler Schappe, Sarah Peskoe, Nrupen Bhavsar, L. Ebony Boulware, Jane Pendergast, Lisa M. McElroy
Journal: JAMA Network Open (2022)

Importance System and center-level interventions to improve health equity in organ transplantation benefit from robust characterization of the referral population served by each transplant center. Transplant referral regions (TRRs) define geographic catchment areas for transplant centers in the US, but accurately characterizing the demographics of populations within TRRs using US Census data poses a challenge. Objective To compare 2 methods of linking US Census data with TRRs—a geospatial intersection method and a zip code cross-reference method. Design, Setting, and Participants This cohort study compared spatial congruence of spatial intersection and zip code cross-reference methods of characterizing TRRs at the census block level. Data included adults aged 18 years and older on the waiting list for kidney transplant from 2008 through 2018. Exposures End-stage kidney disease. Main Outcomes and Measures Multiple assignments, where a census tract or block group crossed the boundary between 2 hospital referral regions and was assigned to multiple different TRRs; misassigned area, the portion of census tracts or block groups assigned to a TRR using either method but fall outside of the TRR boundary. Results In total, 102 TRRs were defined for 238 transplant centers. The zip code cross-reference method resulted in 4627 multiple-assigned census block groups (representing 18% of US land area assigned to TRRs), while the spatial intersection method eliminated this problem. Furthermore, the spatial method resulted in a mean and median reduction in misassigned area of 65% and 83% across all TRRs, respectively, compared with the zip code cross-reference method. Conclusions and Relevance In this study, characterizing populations within TRRs with census block groups provided high spatial resolution, complete coverage of the country, and balanced population counts. A spatial intersection approach avoided errors due to duplicative and incorrect assignments, and allowed more detailed and accurate characterization of the sociodemographics of populations within TRRs; this approach can enrich transplant center knowledge of local referral populations, assist researchers in understanding how social determinants of health may factor into access to transplant, and inform interventions to improve heath equity.
Urine is a viral antigen reservoir in hepatitis E virus infection
Authors: Dong Ying, Qiyu He, Weikun Tian, Yanling Chen, Xiaoping Zhang, Siling Wang, Chang Liu, Zihao Chen, Yu Liu, Lijuan Fu, Li Yan, Ling Wang, Zimin Tang, Lin Wang, Zizheng Zheng, Ningshao Xia
Journal: Hepatology (2022)

HEV ORF2 antigen (Ag) in serum has become a tool for diagnosing current HEV infection. Particularly, urinary shedding of HEV Ag has been gaining increasing interest. We aim to uncover the origin, antigenicity, diagnostic performance, and diagnostic significance of Ag in urine in HEV infection.Clinical serum and urine samples from patients with acute and chronic HEV infection were analyzed for their Ag levels. Ag in urine was analyzed by biochemical and proteomic approaches. The origin of urinary Ag and Ag kinetics during HEV infection was investigated in mouse and rabbit models, respectively. We found that both the Ag level and diagnostic sensitivity in urine were higher than in serum. Antigenic protein in urine was an E2s-like dimer spanning amino acids 453-606. pORF2 entered urine from serum in mice i.v. injected with pORF2. Ag in urine originated from the secreted form of pORF2 (ORF2 S ) that abundantly existed in hepatitis E patients' serum. HEV Ag was specifically taken up by renal cells and was disposed into urine, during which the level of Ag was concentrated >10-fold, resulting in the higher diagnosing sensitivity of urine Ag than serum Ag. Moreover, Ag in urine appeared 6 days earlier, lasted longer than viremia and antigenemia, and showed good concordance with fecal RNA in a rabbit model.Our findings demonstrated the origin and diagnostic value of urine Ag and provided insights into the disposal of exogenous protein of pathogens by the host kidney.
Stem cell membrane-coated abiotic nanomaterials for biomedical applications
Authors: Inês Ferreira-Faria, Satar Yousefiasl, Ana Macário-Soares, Miguel Pereira-Silva, Diana Peixoto, Hajra Zafar, Faisal Raza, Henrique Faneca, Francisco Veiga, Michael R. Hamblin, Franklin R. Tay, Jianqing Gao, Esmaeel Sharifi, Pooyan Makvandi, Ana Cláudia Paiva-Santos
Journal: Journal of Controlled Release (2022)

Nanoscale materials have been extensively employed for diagnostic and therapeutic purposes. However, the developed nanosystems still suffer from some limitations, namely the rapid elimination by the immune system, lack of targeting to specific cells, and insufficient biocompatibility. Therefore, novel strategies based upon a biomimetic approach have received attention to improving the pharmacokinetics and safety profile of nanosystems. One promising strategy is the application of a biomimetic coating consisting of cell membranes derived from different cell types onto nanoparticle cores. Stem cells have been investigated to develop targeted nanodevices owing to their excellent intrinsic tissue-specific homing features, protecting them from the immune system to reach the sites of inflammation. This targeting ability is conferred by a surface repertoire of stem cell-associated biomolecules. Such nanoscopical materials offer sustained circulation and boosted drug accumulation at target sites, augmenting therapeutic efficacy and safety. Additionally, the coating of nanoparticles with cell membranes acts as a camouflage mechanism to increase their circulation time. The current review explores the particular features of stem cell membrane coating as multifunctional biomimetic surface functionalization agents to camouflage nanoparticle cores. Biomedical applications of engineered stem cell membrane-coated nanoparticles, challenges in clinical translation, and their future prospects are addressed.
Analysis of School-Level Vaccination Rates by Race, Ethnicity, and Geography in New York City
Authors: Brian Elbel, Geng Eric Zhou, David C. Lee, Willy Chen, Sophia E. Day, Kevin J. Konty, Amy Ellen Schwartz
Journal: JAMA Network Open (2022)

This cross-sectional study of New York City school data examines differences in COVID-19 vaccination rates by race, ethnicity, and borough.
An Overview of Clinical Development of Agents for Metastatic or Advanced Breast Cancer Without <i>ERBB2</i> Amplification (HER2-Low)
Authors: Aleix Prat, Aditya Bardia, Giuseppe Curigliano, M. Elizabeth H. Hammond, Sibylle Loibl, Sara M. Tolaney, Giuseppe Viale
Journal: JAMA Oncology (2022)

Erb-b2 receptor tyrosine kinase 2 (ERBB2; formerly HER2 [human epidermal growth factor receptor 2]) is an important prognostic and predictive factor in breast cancer. Anti-ERBB2 therapies have improved outcomes in ERBB2-positive breast cancer. However, based on current definitions, tumors with low ERBB2 expression are included in the ERBB2-negative subtype, and therefore, are ineligible for anti-ERBB2 therapies; patients with ERBB2-low (immunohistochemistry [IHC] 1 positive [+] or IHC 2+/in situ hybridization [ISH] negative [-]) tumors account for up to approximately 50% of breast cancer cases. Although the prognostic role of ERBB2-low needs to be defined, ERBB2 offers a potential therapeutic target in these patients.
Pediatric Brain Abscesses, Epidural Empyemas, and Subdural Empyemas Associated with <i>Streptococcus</i> Species — United States, January 2016–August 2022
Authors: Emma K. Accorsi, Sopio Chochua, Heidi L. Moline, Matt Hall, Adam L. Hersh, Samir S. Shah, Amadea Britton, Paulina A. Hawkins, Wei Xing, Jennifer Onukwube Okaro, Lindsay Zielinski, Lesley McGee, Stephanie Schrag, Adam L. Cohen
Journal: MMWR Morbidity and Mortality Weekly Report (2022)

In May 2022, CDC learned of three children in California hospitalized concurrently for brain abscess, epidural empyema, or subdural empyema caused by Streptococcus intermedius. Discussions with clinicians in multiple states raised concerns about a possible increase in pediatric intracranial infections, particularly those caused by Streptococcus bacteria, during the past year and the possible contributing role of SARS-CoV-2 infection (1). Pediatric bacterial brain abscesses, epidural empyemas, and subdural empyemas, rare complications of respiratory infections and sinusitis, are often caused by Streptococcus species but might also be polymicrobial or caused by other genera, such as Staphylococcus. On June 9, CDC asked clinicians and health departments to report possible cases of these conditions and to submit clinical specimens for laboratory testing. Through collaboration with the Children's Hospital Association (CHA), CDC analyzed nationally representative pediatric hospitalizations for brain abscess and empyema. Hospitalizations declined after the onset of the COVID-19 pandemic in March 2020, increased during summer 2021 to a peak in March 2022, and then declined to baseline levels. After the increase in summer 2021, no evidence of higher levels of intensive care unit (ICU) admission, mortality, genetic relatedness of isolates from different patients, or increased antimicrobial resistance of isolates was observed. The peak in cases in March 2022 was consistent with historical seasonal fluctuations observed since 2016. Based on these findings, initial reports from clinicians (1) are consistent with seasonal fluctuations and a redistribution of cases over time during the COVID-19 pandemic. CDC will continue to work with investigation partners to monitor ongoing trends in pediatric brain abscesses and empyemas.